Chronic pain remains a challenge in medical science. Chronic pain is a common complaint in patients who have undergone surgical procedures or who suffer from long term illnesses, such as, e.g., cancer, nerve injury, arthritis, or heart diseases. Existing therapeutic agents for treating chronic pain are often unsatisfactory because of side effects accompanying the treatment. For example, opiates at high doses are apt to produce sedation, respiratory depression, and tolerance, which severely limit their use.
Generally, acute pain is of limited duration and rapidly subsides after removing the triggering stimuli. Acute pain due to the stimulation of intact nociceptors has a protective warning function to preserve physical integrity—the subsequent responses to avoid pain provide protection from injury. Chronic pain typically does not possess this protective function, resulting in a pain disorder. Chronic pain may be subdivided into at least two major groups. Pathophysiological nociceptor pain, including, e.g., chronic inflammatory pain, is caused by stimulation of intact nociceptors, after, for example, tissue trauma. By contrast, neuropathic pain arises from damages to nerves themselves.
The changeover from acute pain to chronic pain may occur within hours. Pain treatment during and following surgery may be affected by this. Acute pain may become chronic, both peripherally and in the CNS, by pathophysiological processes subsequent to tissue damage, for example, after surgery. The association of tissue damage, acute postoperative pain, and development of chronic pain has been investigated. It is possible to regard the severity of acute pain as a predictive factor for the duration of chronic pain. Thus, satisfactory treatment of acute pain is desired.
One issue in combating pain is the side effects of known analgesics, such as, respiratory depression caused by opioids. Since the side effects occasionally result in fatalities in patients having just undergone surgery, pain medications are often not given in sufficient quantity to combat pain satisfactorily. Because of respiratory depression and other known side effects, opiates are often used to an inadequate extent in treating severe pain, for example, in cancer patients. In addition, the risk of respiratory depression occurring after administration of opiates is higher in older people than in younger people. For example, the risk of developing respiratory depression rises distinctly in people of 60 years of age or older.
Thus, there is an urgent need for new therapeutic agents for the treatment of pain, such as, severe pain, with less adverse events than traditional analgesics.